This application proposes to prepare a number of hybridoma cell lines producing monoclonal anti-tumor cell antibodies and to use these reagents to study the mechanism of Antibody Dependent Cell Cytotoxicity (ADCC). Using these homogeneous reagents, it may be possible to clarify some of the present controversy in this area and obtain new information useful in understanding this phenomenon and its importance. In particular, studies would be conducted to determine the effectiveness of various classes and subclasses of antibody and the role of isolated lymphocyte subpopulations in mediating ADCC. The importance of antibody specificity and affinity in these reactions would be determined, as well as differences in the susceptibility to killing of different target cells. The possibility that B2-microglobulin can modulate ADCC reactions would be determined, as well as differences in the susceptibility to killing of different target cells. The possibility that beta2-microglobulin can modulate ADCC reactions would be evaluated. The ability of complexes of defined size antigen-antibody ratio, and class/subclass to arm ADCC effector cells against tumor cells would be determined. Finally, the mechanism by which Fc fragments induce cytotoxicity, the lymphocyte subpopulations involved in this killing, and the effect of these fragments on ADCC reactions would be investigated. It is anticipated that these studies should provide definitive information on some aspects of ADCC reactions and permit a better understanding of the role of this process in immune mechanisms and particularly in tumor immunity. Moreover, some of the information obtained may provide insights into in vivo approaches to the modulation of ADCC reactivity.